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Frontiers in Medicine 2024Childhood blindness is an issue of global health impact, affecting approximately 2 million children worldwide. Vision 2020 and the United Nations Sustainable Development... (Review)
Review
Childhood blindness is an issue of global health impact, affecting approximately 2 million children worldwide. Vision 2020 and the United Nations Sustainable Development Goals previously identified childhood blindness as a key issue in the twentieth century, and while public health measures are underway, the precise etiologies and management require ongoing investigation and care, particularly within resource-limited settings such as sub-Saharan Africa. We systematically reviewed the literature on childhood blindness in West Africa to identify the anatomic classification and etiologies, particularly those causes of childhood blindness with systemic health implications. Treatable causes included cataract, refractive error, and corneal disease. Systemic etiologies identified included measles, rubella, vitamin A deficiency, and Ebola virus disease. While prior public health measures including vitamin A supplementation and vaccination programs have been deployed in most countries with reported data, multiple studies reported preventable or reversible etiologies of blindness and vision impairment. Ongoing research is necessary to standardize reporting for anatomies and/or etiologies of childhood blindness to determine the necessity of further development and implementation of public health measures that would ameliorate childhood blindness and vision impairment.
PubMed: 38439905
DOI: 10.3389/fmed.2024.1349093 -
Cureus Feb 2024Recently, there has been interest in using viruses as cancer treatments. Oncolytic virology was founded by scientists who noticed that viruses might preferentially lyse... (Review)
Review
Recently, there has been interest in using viruses as cancer treatments. Oncolytic virology was founded by scientists who noticed that viruses might preferentially lyse cancer cells over healthy ones. Oncolytic virotherapy has similar obstacles as other treatment approaches, gaining entry into the specific tumour cell, encountering antiviral immune responses, off-target infection and many other unfavourable circumstances in the tumour microenvironment, and a lack of unique therapeutic and predictive biomarkers. However, oncolytic viruses have emerged as the main players in the biological treatment for cancer with the use of vectors such as human adenoviruses in oncolytic virotherapy. Recent large-scale research has shown that other viruses, such as the measles virus and the herpes simplex virus (HSV), may potentially be viable options for cancer treatment. The FDA has cleared T-VEC, an HSV-based oncolytic virus, for use in biological cancer treatment after its successful completion of human clinical trials. Furthermore, the measles virus vaccine strain has shown remarkable outcomes in pre-clinical and clinical testing. The use of such modified viruses in biological cancer treatment holds promise for groundbreaking discoveries in the field of cancer research because of their therapeutic effectiveness, fewer side effects, and safety. Several other newer approaches have been used in recent years. HIV-encoded proteins are also hypothesized to promote mitochondrial homeostasis causing bystander-induced apoptosis. We provide an overview of the most recent developments in the clinical use of oncolytic virus-based biological cancer treatment in this study. This evaluation also assesses the advantages and disadvantages of the viral candidates and provides insight into their potential in the future.
PubMed: 38435173
DOI: 10.7759/cureus.53431 -
Euro Surveillance : Bulletin Europeen... Feb 2024We report on an ongoing measles outbreak in the Federation of Bosnia and Herzegovina with 141 cases notified between week 52 2023 and week 6 2024. Among those with known...
We report on an ongoing measles outbreak in the Federation of Bosnia and Herzegovina with 141 cases notified between week 52 2023 and week 6 2024. Among those with known vaccination status, 97% were unvaccinated and the most affected group is children under the age of 5 years (n = 87) who were not vaccinated during the pandemic years. Sixty-eight cases were hospitalised, the most common complications were measles-related pneumonia and diarrhoea. The sequenced measles viruses from four cases belonged to genotype D8.
Topics: Child; Humans; Child, Preschool; Vaccination; Bosnia and Herzegovina; Measles; Measles virus; Disease Outbreaks; Exanthema
PubMed: 38426241
DOI: 10.2807/1560-7917.ES.2024.29.9.2400107 -
JCO Global Oncology Feb 2024To share our clinical experience with the diagnosis and management of children with hematolymphoid malignancies presenting with epilepsia partialis continua (EPC) as a...
PURPOSE
To share our clinical experience with the diagnosis and management of children with hematolymphoid malignancies presenting with epilepsia partialis continua (EPC) as a sequelae of measles infection.
MATERIALS AND METHODS
In December 2022, a series of children in our hemato-oncology unit presented with focal status epilepticus with no conclusive evidence pointing toward any underlying etiology. One such child had a typical measles rash a few weeks before the onset of this focal status epilepticus. After a series of cases with a similar presentation, a clinical pattern suspicious for measles became evident. cerebrospinal fluid polymerase chain reaction was positive for measles virus with measles immunoglobin M detected in the serum. This led to the diagnosis of measles inclusion-body encephalitis in a series of children who presented with EPC over a period of 3 months. EPC is a rare manifestation of measles that is seen only in immunocompromised patients.
RESULTS
Among the 18 children reported in this series, only 10 had a history of rashes. The rash was mostly transient and elicited only on retrospective history taking. Five of the 18 children who did not lose consciousness during the prolonged seizure episode survived the disease but had residual neurologic sequelae. Among the 18 children, two were unimmunized and immunization status could not be confirmed in three other children.
CONCLUSION
This case series highlights the threats posed by measles infection in children with cancer who are immunosuppressed because of the underlying disease and ongoing chemotherapy. Loss of herd immunity because of declining measles immunization rates secondary to vaccine hesitancy and COVID-19 lockdown pose a greater risk of measles infection and its complications for patients with deficient immune systems.
Topics: Child; Humans; Retrospective Studies; Epilepsia Partialis Continua; Measles; Neoplasms; Disease Progression; Exanthema
PubMed: 38422460
DOI: 10.1200/GO.23.00399 -
Journal of Virology Mar 2024Morbilliviruses are members of the family Paramyxoviridae and are known for their ability to cause systemic disease in a variety of mammalian hosts. The prototypic...
Morbilliviruses are members of the family Paramyxoviridae and are known for their ability to cause systemic disease in a variety of mammalian hosts. The prototypic morbillivirus, measles virus (MeV), infects humans and still causes morbidity and mortality in unvaccinated children and young adults. Experimental infection studies in non-human primates have contributed to the understanding of measles pathogenesis. However, ethical restrictions call for the development of new animal models. Canine distemper virus (CDV) infects a wide range of animals, including ferrets, and its pathogenesis shares many features with measles. However, wild-type CDV infection is almost always lethal, while MeV infection is usually self-limiting. Here, we made five recombinant CDVs, predicted to be attenuated, and compared their pathogenesis to the non-attenuated recombinant CDV in a ferret model. Three viruses were insufficiently attenuated based on clinical signs, fatality, and systemic infection, while one virus was too attenuated. The last candidate virus caused a self-limiting infection associated with transient viremia and viral dissemination to all lymphoid tissues, was shed transiently from the upper respiratory tract, and did not result in acute neurological signs. Additionally, an in-depth phenotyping of the infected white blood cells showed lower infection percentages in all lymphocyte subsets when compared to the non-attenuated CDV. In conclusion, infection models using this candidate virus mimic measles and can be used to study pathogenesis-related questions and to test interventions for morbilliviruses in a natural host species.IMPORTANCEMorbilliviruses are transmitted via the respiratory route but cause systemic disease. The viruses use two cellular receptors to infect myeloid, lymphoid, and epithelial cells. Measles virus (MeV) remains an important cause of morbidity and mortality in humans, requiring animal models to study pathogenesis or intervention strategies. Experimental MeV infections in non-human primates are restricted by ethical and practical constraints, and animal morbillivirus infections in natural host species have been considered as alternatives. Inoculation of ferrets with wild-type canine distemper virus (CDV) has been used for this purpose, but in most cases, the virus overwhelms the immune system and causes highly lethal disease. Introduction of an additional transcription unit and an additional attenuating point mutation in the polymerase yielded a candidate virus that caused self-limiting disease with transient viremia and virus shedding. This rationally attenuated CDV strain can be used for experimental morbillivirus infections in ferrets that reflect measles in humans.
Topics: Animals; Dogs; Humans; Disease Models, Animal; Distemper; Distemper Virus, Canine; Ferrets; Measles; Measles virus; Morbillivirus; Morbillivirus Infections; Primates; Viremia
PubMed: 38415596
DOI: 10.1128/jvi.01850-23 -
Vaccine Mar 2024Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who...
Neutralizing antibody titers against D8 genotype and persistence of measles humoral and cell-mediated immunity eight years after the first dose of measles, mumps, and rubella vaccine in Brazilian children.
OBJECTIVE
Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who received their first dose of the measles, mumps, and rubella vaccine eight years previously.
METHODS
Measles-specific IgG and neutralizing antibodies were determined in serum using ELISA and plaque reduction neutralization test, respectively. Cellular response was evaluated from peripheral blood mononuclear cells (PBMC). IFN-γ-secreting cells, memory B and T cells, and immunological mediators were assayed by ELISpot, flow cytometry, and multiplex liquid microarray assay, respectively.
RESULTS
Antibody concentrations declined over time; however, the vaccine-induced neutralizing antibodies' effect against D8 and vaccinal genotypes persisted. PBMC stimulated with the vaccine virus exhibited specific IFN- γ-measles-secreting responses in most participants. Participants with high levels of neutralizing antibodies showed a higher proportion of activated B cells compared to participants with low levels of neutralizing antibodies, while proportions of memory CD4+ and CD8+ T cells were similar between these groups. PBMC supernatant cytokine levels showed a significant difference between stimulated and non-stimulated conditions for IL-2, TNF-α, IL-10, and CXCL10.
CONCLUSION
Despite the decline in antibody concentrations over time, the participants still demonstrated neutralizing capacity against the measles D8 genotype five to eight years after the second dose of the measles, mumps, and rubella vaccine. Additionally, most of the enrolled children exhibited cell-mediated immunity responses to measles virus stimulation.
Topics: Child; Humans; Mumps; Leukocytes, Mononuclear; Measles-Mumps-Rubella Vaccine; Brazil; Antibodies, Viral; Measles; Antibodies, Neutralizing; Measles Vaccine; Immunity, Cellular; Rubella
PubMed: 38413280
DOI: 10.1016/j.vaccine.2024.02.060 -
MBio Apr 2024The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak took the world by storm due to its rapid global spread and unpredictable disease outcomes. The...
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak took the world by storm due to its rapid global spread and unpredictable disease outcomes. The extraordinary ascension of SARS-CoV-2 to pandemic status motivated a world-wide effort to rapidly develop vaccines that could effectively suppress virus spread and mitigate severe disease. These efforts culminated in the development and deployment of several highly effective vaccines that were heralded as the beginning-of-the-end of the pandemic. However, these successes were short lived due to the unexpected and continuous emergence of more transmissible and immune-evasive SARS-CoV-2 variants. Thus, attention has shifted toward developing novel vaccine platforms that elicit more robust and sustained neutralizing antibody responses. Recent findings by Muñoz-Alía and colleagues address this by combining a live recombinant measles vaccine platform with novel biochemical approaches to generate vaccine candidates that bolster the potency of neutralizing antibody responses against diverse SARS-CoV-2 spike proteins (M. Á. Muñoz-Alía, R. A. Nace, B. Balakrishnan, L. Zhang, et al., mBio 9:e02928-23, 2024, https://doi.org/10.1128/mbio.02928-23).
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19; Measles Vaccine; Measles; Antibodies, Neutralizing; Glycoproteins
PubMed: 38407097
DOI: 10.1128/mbio.00067-24 -
BioRxiv : the Preprint Server For... May 2024Negative sense RNA viruses (NSV) include some of the most detrimental human pathogens, including the influenza, Ebola and measles viruses. NSV genomes consist of one or...
Negative sense RNA viruses (NSV) include some of the most detrimental human pathogens, including the influenza, Ebola and measles viruses. NSV genomes consist of one or multiple single-stranded RNA molecules that are encapsidated into one or more ribonucleoprotein (RNP) complexes. These RNPs consist of viral RNA, a viral RNA polymerase, and many copies of the viral nucleoprotein (NP). Current evolutionary relationships within the NSV phylum are based on alignment of conserved RNA-directed RNA polymerase (RdRp) domain amino acid sequences. However, the RdRp domain-based phylogeny does not address whether NP, the other core protein in the NSV genome, evolved along the same trajectory or whether several RdRp-NP pairs evolved through convergent evolution in the segmented and non-segmented NSV genomes architectures. Addressing how NP and the RdRp domain evolved may help us better understand NSV diversity. Since NP sequences are too short to infer robust phylogenetic relationships, we here used experimentally-obtained and AlphaFold 2.0-predicted NP structures to probe whether evolutionary relationships can be estimated using NSV NP sequences. Following flexible structure alignments of modeled structures, we find that the structural homology of the NSV NPs reveals phylogenetic clusters that are consistent with RdRp-based clustering. In addition, we were able to assign viruses for which RdRp sequences are currently missing to phylogenetic clusters based on the available NP sequence. Both our RdRp-based and NP-based relationships deviate from the current NSV classification of the segmented , which cluster with the other segmented NSVs in our analysis. Overall, our results suggest that the NSV RdRp and NP genes largely evolved along similar trajectories and that even short pieces of genetic, protein-coding information can be used to infer evolutionary relationships, potentially making metagenomic analyses more valuable.
PubMed: 38405982
DOI: 10.1101/2024.02.16.580771 -
Indian Journal of Pathology &... Nov 2023The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate...
BACKGROUND
The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age.
MATERIAL AND METHODS
The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR.
RESULTS
Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases.
CONCLUSION
We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.
PubMed: 38394398
DOI: 10.4103/ijpm.ijpm_60_23